Category: Safety monitoring

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COVID-19 Vaccine Janssen Johnson & Johnson Safety monitoring

Johnson & Johnson (Janssen) Vaccine: April 2021

Bottom Line About Rare Blood Clots With Johnson & Johnson (Janssen) COVID-19 Vaccine

    • The Johnson & Johnson (Janssen) COVID-19 vaccine appears to increase the risk of developing rare blood clots, combined with low platelet counts. The medical term for this condition is Thrombosis with Thrombocytopenia Syndrome (TTS).
    • As of April 12, 2021, nearly 7 million people had received this vaccine in the United States.
    • As of April 21, 2021, 15 people who had received the vaccine developed TTS and 3 of these people died.
    • The risk of developing TTS following vaccination is very low. For every 1 million women between 18 and 49 years old, about 7 developed TTS. The risk is even lower among older women and men of any age.
    •  Analyses performed by scientists at the Center for Disease Control and Prevention (CDC) estimated that the risk of dying of COVID-19 is greater than the risk of developing TTS after receiving the Johnson & Johnson (Janssen) vaccine. Therefore, they continue to believe that the benefits of the vaccine outweigh the risks.
    • The small risk of TTS can be avoided by being vaccinated with either the Pfizer/BioNTech or Moderna vaccines. (No cases of TTS have been observed among people who have received the Pfizer/BioNTech or Moderna vaccines. Over 180 million doses of these vaccines have been administered in the US.)
    •  CDC encourages health care providers to talk to women between the ages of 18 and 49 about the risk of TTS with the Johnson & Johnson (Janssen) vaccine and to discuss the possibility of using one of the other approved COVID-19 vaccines instead. However, if a woman is unable to use either of the other vaccines or prefers a vaccine that only requires one shot, both the FDA and CDC considers the Johnson & Johnson (Janssen) vaccine safe and effective to use.
    • CDC continues to emphasize that vaccines save lives and encourages all adults to be vaccinated.

April 13 – April 23, 2021: On April 13th, the US Food and Drug Administration (FDA) recommended a pause in use of the Johnson & Johnson (Janssen) COVID-19 vaccine that received an Emergency Use Authorization in the US on February 27, 2021. As of April 12, 2021, more than 6.8 million doses of this vaccine had been administered. The pause was recommended in response to 6 cases of a rare type of blood clot (cerebral venous sinus thrombosis, CVST) combined with low platelet counts. The medical term for this condition is Thrombosis with Thrombocytopenia Syndrome (TTS). All six cases occurred in women between 18 and 48 years old within two weeks following vaccination with the Johnson & Johnson (Janssen) vaccine.

A drug called heparin is usually used to treat blood clots. However, heparin can make TTS worse. The purpose of the pause was 2-fold. First, it allowed time for the FDA and Centers for Disease Control and Prevention (CDC) to make both patients and health care providers aware of this condition, including symptoms of a possible clot, the importance of early diagnosis and treatment, and treatments to implement (and those to avoid).

Currently, CDC recommends that people who receive the Johnson & Johnson (Janssen) vaccine, should be on the lookout for the following symptoms of a possible clot for three weeks after receiving the vaccine and should seek medical care right away if they develop any of these symptoms. The symptoms to watch for include: severe or persistent headaches or blurred vision, shortness of breath, chest pain, leg swelling, persistent abdominal pain, and easy bruising or tiny blood spots under the skin beyond the injection site

The second reason for the pause is that it gave the FDA and CDC time to review the cases that had been identified and determine the best way to proceed. Since April 13th, two emergency meetings of CDC’s Advisory Committee on Immunization Practices (ACIP) have been held. Both of these meetings were open to the public and live-streamed. Links to materials from these meetings are provided below.

At the end of the meeting on April 23rd, the Committee recommended that use of the Johnson & Johnson (Janssen) vaccine resume in the United States without any age or sex restrictions. This recommendation was based on data concerning the risks and benefits associated with different vaccination strategies (e.g., limiting use of the vaccine to older adults), as well as the feasibility of implementing different strategies on a nationwide basis in the midst of the current global pandemic.

TTS is a very rare condition, affecting only 0.7 to 1.6 people per million in the US each year. Although the mechanism of action is not clear, it is likely that the Johnson & Johnson (Janssen) vaccine increases the risk of developing TTS. However, the likelihood of developing TTS following vaccination is very small.

As of April 21, 2021, a total of 15 cases of TTS had been confirmed among the nearly 8 million people who had received the Johnson & Johnson (Janssen) vaccine. All of these cases occurred within about two weeks following vaccination. As of April 21st, 3 of the 15 people who developed TTS following vaccination had died and 4 remained hospitalized in an intensive care unit. (For comparison, no cases of TTS have been reported following the administration of the Pfizer/BioNTech or Moderna vaccines. As of April 21st, over 180 million doses of these vaccines had been administered in the US.)

As shown in the table below, most of the 15 cases of TTS occurred among women between the ages of 18 and 49. In this group, 7.0 cases of TTS were reported for every 1 million doses of the Johnson & Johnson (Janssen) vaccine administered. Thus, even in this group, the likelihood of developing TTS following vaccination is very small.

Given this serious (but rare) risk, the question becomes whether the benefits associated with the Johnson & Johnson (Janssen) vaccine outweigh the risks. From a public health perspective, the answer is pretty clear. As shown in the table below, CDC scientists estimated that continuing to use the Johnson & Johnson (Janssen) vaccine for adults age 18 years and older would prevent 586 to 1,435 deaths due to COVID-19, while causing only 26 cases of TTS. The deaths prevented are the result of being able to vaccinate all interested adults more quickly than if only the Pfizer/BioNTech and Moderna vaccines were available.

CDC scientists also examined vaccine risks/benefits separately for younger women, older women, younger men, and older men. These analyses assumed that the people did not receive one of the other COVID-19 vaccines available in the US. As shown in the table below, the benefit/risk ratio was smallest for women in the younger age group.

At the end of the meeting on April 23rd, the Committee recommended that use of the Johnson & Johnson (Janssen) vaccine resume in the US without any age or sex restrictions. However, it was understood that the FDA would add a warning statement about the risk of TTS in materials distributed to patients and health care providers. In addition, CDC recommends that for females under the age of 50 health care providers discuss the option of receiving either the Pfizer/BioNTech vaccine or the Moderna vaccine instead of the Johnson & Johnson vaccine. They also emphasized that the risk of TTS is very low and that it is important for all individuals to be vaccinated. For individuals who are unable to receive one of the other vaccines or who cannot complete the 2-dose series required for both the Pfizer/BioNTech and Moderna vaccines, experts believe that the potential benefits of the Johnson & Johnson (Janssen) vaccine outweigh the known and potential risks.

In conclusion, the ability of FDA and CDC scientists to quickly identify the very rare risk of TTS should reassure the public that surveillance systems such as the Vaccine Adverse Event Reporting System (VAERS) are working the way they should. Very rare adverse events are almost impossible to discover in clinical trials because they may not occur in even large trials involving tens of thousands of people. Once the possible risk of TTS was identified, the FDA and CDC worked together to implement a pause in use of the Johnson & Johnson (Janssen) vaccine, educate the public and health care providers about the potential risk of TTS, and implement an emergency review process by independent scientists before moving forward. This review process was transparent. Committee meetings were open to the public and all meeting materials remain available online. We applaud the FDA and CDC for their work to review the evidence and chart a course forward that is likely to prevent thousands of deaths over the coming months.

Other References:

Slides used in the scientific presentations made during the meeting on April 14th can be found here. The meeting can be viewed in full using the following links: Welcome & Coronavirus Disease 2019 (COVID-19) Vaccines and Public Comment & Vote. 

Slides used in the scientific presentations made during the meeting on April 23rd can be found here. It can be viewed in full using the following links: Welcome & Coronavirus Disease 2019 (COVID-19) Vaccines, Public Comment , and Janssen COVID-19 vaccine. 

The revised Fact Sheet for Healthcare Providers Administering Vaccine can be obtained here. This fact sheet now includes a warning about TTS.

A fact sheet for patients prepared by CDC can be found here.

A paper published in Morbidity and Mortality Weekly Report (MMRW) discussing the risk of TTS following administration of the Johnson & Johnson (Janssen) vaccine can be found here.

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BioNTech Moderna Pfizer Safety monitoring

Safety Monitoring Updates (March 1, 2021)

At the March 1, 2021 meeting of the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), Dr. Tom Shimabukuro, a member of the CDC COVID-19 Vaccine Task Force, provided a safety update on the COVID-19 vaccines from Pfizer-BioNTech and Moderna. This safety update was based on information reported to CDC by both health care providers and people who had received one or two doses of the vaccines as of February 16, 2021. By this date, 55.2 million vaccine doses had been administered in the U.S. Overall, the safety profile of COVID-19 vaccines continues to be reassuring and consistent with safety data observed from the pre-authorization clinical trials. In addition, no unexpected pregnancy or infant outcomes have been observed related to COVID-19 vaccination during pregnancy.

CDC has a comprehensive COVID-10 vaccine safety monitoring system in place to conduct post-marketing surveillance of COVID-19 vaccines following the issuance of emergency use authorizations (EUAs). The EUAs for the Pfizer-BioNTech and Moderna vaccines were issued on December 11 and 18, 2020, respectively. The presentation at the ACIP meeting on March 1st reported on vaccine safety data from several monitoring programs including v-safe, the Vaccine Adverse Event Reporting System (VAERS), and the Vaccine Safety Datalink (VSD) platform as noted below. Additional information about ongoing efforts to ensure COVID-19 vaccine safety can be found on websites maintained by CDC and FDA.

V-safe is a smartphone based “after vaccination health checker” where people who have received a COVID-19 vaccine can quickly tell CDC about any side effects they experienced. An analysis of safety data collected by the v-safe program during the first month of administration of the Pfizer-BioNTech and Moderna vaccines (December 14 – January 13) was published on February 19th in CDC Morbidity and Mortality Weekly Report (MMWR). Side effects (such as injection site pain, headache, fatigue, and muscle soreness) were similar for both the Pfizer-BioNTech and Moderna vaccines and consistent with those reported in the Phase 3 clinical trials.

The Vaccine Adverse Event Reporting System (VAERS) accepts reports from everyone regardless of the whether the vaccine caused the side effect or the level of clinical seriousness of the event. However, VAERS can rapidly detect safety “signals” and rare adverse events that warrant further investigation. Among the 105,000 COVID-19 vaccine-related adverse effects reported to VAERS as of February 16th, 94% were non-serious and 6% were serious (similar to experience with influenza vaccines). The most common side effects reported were headache, fatigue, fever, dizziness, chills, and pain at injection site, with no new safety concerns noted. Anaphylaxis continues to be a rare occurrence, with an estimated 2.5 cases per million doses administered for the Moderna vaccine, and 4.7 cases per million doses administered for the Pfizer-BioNTech vaccine as reported in the Journal of the American Medical Association .

CDC also utilizes Vaccine Safety Datalink (VSD), a collaborative project with nine health care organizations across the country to monitor possible adverse events when new vaccines are licensed (or authorized for emergency use such as for the current COVID-19 vaccines). Notably, CDC can assess if the rate of adverse events among vaccinated people is higher than among a comparison unvaccinated group; a higher rate of specific adverse events in vaccinated people may represent a “safety signal” that needs further attention. As of February 13, 2021, no such safety signals were detected among people vaccinated with either the Pfizer-BioNTech or Moderna vaccines as compared to the unvaccinated population.

More than 30,000 pregnant women who received either the Pfizer-BioNTech or Moderna COVID-19 vaccines have registered in the v-safe program. The side effect profile and adverse events observed among pregnant women did not indicate any safety issues, and most reports to the VAERS system among pregnant women involved non-pregnancy-specific side effects (local or systemic effects like injection-site pain, headache, fatigue, and muscle soreness). Pregnancy-specific adverse events such as miscarriage were within the known background rates for unvaccinated women.

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BioNTech Moderna Pfizer Safety monitoring

Safety Monitoring Updates (February 15, 2021)

The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for the COVID-19 vaccines from Pfizer-BioNTech (December 11, 2020) and Moderna (December 18, 2020). At the January 27, 2021 meeting of the Center for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), a member of CDC’s vaccine safety team provided a safety update on both vaccines based on information reported to CDC by both health care providers and people who had received one or two doses of the vaccines as of January 14, 2021. By this date, 23.4 million vaccine doses had been administered in the U.S. Overall, the safety profiles of COVID-19 vaccines are reassuring and consistent with safety data observed from the pre-authorization clinical trials.

CDC and the FDA use several mechanisms and databases for the ongoing collection and evaluation of COVID-19 vaccine safety data as these new vaccines are administered across the U.S.  A comprehensive, COVID-10 vaccine safety monitoring system was put in place by CDC to conduct post-marketing surveillance of COVID-19 vaccines following the issuance of EUAs. The presentation at the ACIP meeting on January 27 reported on vaccine safety data from several monitoring programs including v-safe, the Vaccine Adverse Event Reporting System (VAERS), and the Vaccine Safety Datalink (VSD) platform as noted below. In addition, Pfizer-BioNTech  and Moderna must submit periodic vaccine safety reports to the FDA  and report serious adverse events to VAERS.

The smartphone-based v-safe is an “after vaccination health checker” where people who have received a COVID-19 vaccine can quickly tell CDC about any side effects they experienced. Based on information reported to v-safe as of January 14, side effects (such as headache, fatigue and muscle soreness)  reported have been similar to those reported in the Phase 3 clinical trials.

Another mechanism to capture side effect information for vaccines is the Vaccine Adverse Event Reporting System (VAERS) which is co-managed by CDC and the FDA. VAERS accepts reports from everyone regardless of the whether the vaccine caused the side effect or the level of clinical seriousness of the event. However, VAERS can rapidly detect safety “signals” and rare adverse events that warrant further investigation.   The most reported adverse events for either the Pfizer-BioNTech or Moderna vaccines as of January 18 included headache, fatigue, fever, dizziness, chills, and pain, like the most frequent side effects reported in the v-safe platform.  Concerning the rare occurrence of anaphylaxis following vaccine administration, the available data indicate that 5.0 cases of anaphylaxis have occurred for every one million doses of the Pfizer-BioNTech vaccine administered and 2.8 cases have occurred for every one million doses of the Moderna vaccine administered.

CDC also utilizes the Vaccine Safety Datalink (VSD), a collaborative project with nine health care organizations across the country to monitor possible adverse events when new vaccines are licensed (or authorized for emergency use such as for the current COVID-19 vaccines). Notably, CDC can assess if the rate of adverse events among vaccinated people is higher than among a comparison unvaccinated group; a higher rate of specific adverse events in vaccinated people may represent a “safety signal” that needs further attention. As of January 16, 2021, no such safety signals were detected among people vaccinated with either the Pfizer-BioNTech or Moderna vaccines as compared to the unvaccinated population. While the Phase 3 studies of both vaccines noted a few more cases of Bell’s Palsy occurring in the vaccinated groups vs. the placebo arms, Bell’s Palsy did not represent a safety signal in the VSD analysis.  There were no reported cases of anaphylaxis in the VSD analysis among those vaccinated with either vaccine.